Type 2 Diabetes Mellitus
Conditions
Keywords
Type 2 Diabetes Mellitus, Saxagliptin, Randomised, Double-blind
Brief summary
The study will evaluate the efficacy and tolerability of saxagliptin compared to uptitration of metformin in patients with type 2 diabetes who have inadequate glycaemic control on a submaximal dose of metformin.
Interventions
DRUGSaxagliptin
5 mg, oral tablet, once daily
DRUGMetformin
500 mg, oral tablet, 1 or 2 additional tablets per day added to background therapy
Sponsors
Bristol-Myers Squibb
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of signed informed consent * Established clinical diagnosis of type 2 diabetes. Treatment with a stable dose of metformin monotherapy (1500-1700 mg/day) for at least 8 weeks prior to visit 1. * HbA1c ≥7.0% and ≤10.0%
Exclusion criteria
* Type 1 diabetes, history of diabetic ketoacidosis or hyperosmolar non-ketonic coma. * Renal impairment as defined by a creatinine clearance \<60 mL/min/1.73 m2 * Individuals who, in the opinion of the investigator, in which participation in this study may pose a significant risk to the patient and could render the patient unable to successfully complete the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Absolute Change From Baseline in HbA1c at Week 24 | Baseline and 24 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Achieving a Therapeutic Response at Week 24 Defined as HbA1c<7.0% | 24 Weeks | Proportion, percentage of patients in each treatment group, achieving therapeutic response, HbA1c below 7.0 percent |
| Proportion of Patients Achieving a Therapeutic Response at Week 24 Defined as HbA1c<=6.5% | 24 Weeks | Proportion, percentage of patients in each treatment group, achieving therapeutic response, HbA1c below or equal to 6.5 percent |
| Change From Baseline to Week 24 in Fasting Plasma Glucose | Baseline and 24 weeks | — |
| Change From Baseline to Week 24 in Fasting Insulin | Baseline and 24 weeks | — |
| Change From Baseline to Week 24 in Beta-cell Function as Measured by Homeostasis Model Assessment-2-beta | Baseline and 24 weeks | — |
Countries
Belgium, France, Germany, Italy, Spain, Turkey (Türkiye), United Kingdom
Participant flow
Recruitment details
The study was conducted at hospital clinics and general practitioners. Patient recruitment started October 20, 2009 and was completed April 30, 2010
Pre-assignment details
Screening, enrollment (2 weeks) and lead-in period (4 weeks). Main reason for not being randomised was due to renal function not meeting inclusion criteria. (Samples taken and analysed after enrollment into the study but prior to randomisation).
Participants by arm
| Arm | Count |
|---|---|
| Saxagliptin Saxagliptin, 5 mg once daily add-on to Metformin 1500 mg/day | 147 |
| Metformin Uptitration Metformin uptitration, 500-1000 mg daily , add-on to Metformin 1500 mg/day | 139 |
| Total | 286 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Other | 3 | 2 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Study specific discontinuation criteria | 16 | 23 |
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | Saxagliptin | Metformin Uptitration | Total |
|---|---|---|---|
| Age Continuous | 58.7 Years STANDARD_DEVIATION 11.31 | 58.6 Years STANDARD_DEVIATION 9.79 | 58.7 Years STANDARD_DEVIATION 10.58 |
| Sex: Female, Male Female | 59 Participants | 63 Participants | 122 Participants |
| Sex: Female, Male Male | 88 Participants | 76 Participants | 164 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 27 / 147 | 22 / 139 |
| serious Total, serious adverse events | 6 / 147 | 6 / 139 |
Outcome results
Primary
Absolute Change From Baseline in HbA1c at Week 24
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saxagliptin | Absolute Change From Baseline in HbA1c at Week 24 | -0.47 Percent (%) | Standard Error 0.06 |
| Metformin Uptitration | Absolute Change From Baseline in HbA1c at Week 24 | -0.38 Percent (%) | Standard Error 0.06 |
Comparison: The null hypothesis H0: µt-µC=0, where μT denotes the mean absolute change in HbA1c from baseline to Week 24 in the group of patients treated with saxagliptin (test medication, T) and μC the mean absolute change in HbA1c from baseline to Week 24 in the group of patients with uptitration of metformin (comparator, C) A sample size of 120 randomized and treated patients per treatment group yielded 80% power under the assumption of a true treatment difference of 0.4% and a standard deviation of 1.1%p-value: 0.2695% CI: [-0.26, 0.07]ANCOVA
Secondary
Change From Baseline to Week 24 in Beta-cell Function as Measured by Homeostasis Model Assessment-2-beta
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saxagliptin | Change From Baseline to Week 24 in Beta-cell Function as Measured by Homeostasis Model Assessment-2-beta | 4.70 Percent (%) | Standard Error 3.01 |
| Metformin Uptitration | Change From Baseline to Week 24 in Beta-cell Function as Measured by Homeostasis Model Assessment-2-beta | 2.34 Percent (%) | Standard Error 3.13 |
p-value: 0.588295% CI: [-6.22, 10.93]ANCOVA
Secondary
Change From Baseline to Week 24 in Fasting Insulin
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saxagliptin | Change From Baseline to Week 24 in Fasting Insulin | -1.9 microUnit/milliLiter | Standard Error 0.82 |
| Metformin Uptitration | Change From Baseline to Week 24 in Fasting Insulin | -2.3 microUnit/milliLiter | Standard Error 0.85 |
p-value: 0.770195% CI: [-2, 2.7]ANCOVA
Secondary
Change From Baseline to Week 24 in Fasting Plasma Glucose
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saxagliptin | Change From Baseline to Week 24 in Fasting Plasma Glucose | -1.07 millimol/Liter | Standard Error 0.16 |
| Metformin Uptitration | Change From Baseline to Week 24 in Fasting Plasma Glucose | -1.14 millimol/Liter | Standard Error 0.17 |
p-value: 0.762795% CI: [-0.38, 0.52]ANCOVA
Secondary
Proportion of Patients Achieving a Therapeutic Response at Week 24 Defined as HbA1c<=6.5%
Proportion, percentage of patients in each treatment group, achieving therapeutic response, HbA1c below or equal to 6.5 percent
Time frame: 24 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saxagliptin | Proportion of Patients Achieving a Therapeutic Response at Week 24 Defined as HbA1c<=6.5% | 20.5 Percentage of patients |
| Metformin Uptitration | Proportion of Patients Achieving a Therapeutic Response at Week 24 Defined as HbA1c<=6.5% | 16.8 Percentage of patients |
p-value: 0.620395% CI: [-6.7, 11.3]Regression, Logistic
Secondary
Proportion of Patients Achieving a Therapeutic Response at Week 24 Defined as HbA1c<7.0%
Proportion, percentage of patients in each treatment group, achieving therapeutic response, HbA1c below 7.0 percent
Time frame: 24 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saxagliptin | Proportion of Patients Achieving a Therapeutic Response at Week 24 Defined as HbA1c<7.0% | 43.8 Percentage of patients |
| Metformin Uptitration | Proportion of Patients Achieving a Therapeutic Response at Week 24 Defined as HbA1c<7.0% | 35.0 Percentage of patients |
p-value: 0.320295% CI: [-5.6, 17.1]Regression, Logistic